Fig. 5: The physiological role of MSL2.
a, Schematic of the Msl2-null allele of the Msl2−/− mice in the pure C57BL/6 background, showing the two Msl2 transcripts, and the predicted outcome of CRISPR-mediated deletion in exon e1 (red) on the MSL2 protein. The asterisk depicts an alternative exon in isoform 2. b, Genotype ratios in prenatal (E11.5–18.5) or postnatal (P0.5) litters of Msl2+/− female (F) mice mated with Msl2+/− male (M) mice. n = 195 (prenatal) and n = 37 (postnatal). All animal numbers are provided in the Source Data. c, The percentage and number of E18.5 embryos with severe, mild or no phenotypes isolated from Msl2+/− female mice mated with Msl2+/− male mice. d, The phenotypes of the indicated genotypes in E18.5 embryos isolated from Msl2+/− female mice mated with Msl2+/− male mice. e, Representative images of Msl2+/− and Msl2−/− E18.5 embryo heads with eye malformations (left). The arrows highlight the affected eyes. Right, other severe phenotypes observed in Msl2−/− female E18.5 embryos, including brain defects, microphthalmia, haemorrhage (black arrows) and kidney malformation (white arrow) are indicated. f, Comparison of downregulated genes in the brain and placenta of female Msl2−/− E18.5 embryos (n = 3 and 3 (Msl2+/+); n = 3 and 2 (Msl2−/−)) scored at FDR < 0.05 and log2[FC] < 0. The colour key indicates the log2[FC] (KO/WT). g, GO enrichment analysis of downregulated genes in the brain and placenta (f) of female Msl2−/− E18.5 embryos. The ratio of genes in each category is indicated by the dot size and the adjusted P value is indicated by the colour range. h,i, Expression changes of bi-to-mono (h) and haploinsufficient genes (i) of four NPCs in Msl2−/− E18 embryos. The log2[FC] (KO/WT) (standard analysis) of NPCs, brain and placenta is shown. The percentages of bi-to-mono (h) and haploinsufficient genes (i) with consistent changes in the brains are shown. The colour key indicates the log2[FC] (KO/WT). j, Model summarizing MSL2-mediated transition of biallelic to monoallelic expression in hybrid NPCs. The diagrams in a and j were created using BioRender.
